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Journal of Molecular Endocrinology (2007) 39 289-304    DOI: 10.1677/JME-07-0043
© 2007 Society for Endocrinology
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Role of specificity protein transcription factors in estrogen-induced gene expression in MCF-7 breast cancer cells

 Shaheen Khan1, Fei Wu2, Shengxi Liu3, Qian Wu2 and Stephen Safe1,3

Departments of 1 Veterinary Physiology and Pharmacology and 2 Biochemistry and Biophysics,, Texas A & M University, College Station, Texas 77843-4466, USA 3 The Institute of Biosciences and Technology,, Texas A & M University Health Science Center, 2121 West Holcombe Boulevard, Houston, Texas 77030, USA

(Correspondence should be addressed to S Safe; Email: ssafe{at}cvm.tamu.edu)

The authors have nothing to disclose.

Deletion analysis of several 17ß-estradiol (E2)-responsive genes have identified GC-rich sites that are associated with hormone-induced transactivation in MCF-7 breast cancer cells. However, the role of individual specificity proteins (Sps) in mediating hormone-induced gene expression has not been unequivocally determined. In transient transfection studies using E2-responsive GC-rich promoters from the E2F1, carbamoylphosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD), and retinoic acid receptor {alpha} (RAR{alpha}) genes, RNA interference using small inhibitory RNAs for Sp1 (iSp1), Sp3 (iSp3), and Sp4 (iSp4) decreased both basal and E2-induced transactivation. The contributions of individual Sp proteins to basal and E2-induced activity were promoter dependent. iSp1, iSp3, and iSp4 also significantly inhibited hormonal induction of E2F1, CAD, and RAR{alpha} mRNA levels; however, the enhanced inhibitory effects of the latter two small inhibitory RNAs suggest that Sp3 and Sp4 play a major role in estrogen receptor {alpha}/Sp-mediated gene expression in MCF-7 cells.




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